Abnormal cell surface properties characterize leukocytes from several puzzling human diseases, including Chediak-Higashi syndrome, glutathione synthetase deficiency and Severe Combined Immune Deficiency. We have identified abnormal microtubule or microfilament properties that may explain the abnormal surface properties of these cells. We are now seeking the biochemical basis for the cytoskeletal-membrane defects. In particular we emphasize the role of purine compounds in microtubule assembly, and the role of glutathione metabolism in microtubule disasembly. We will also continue to define and catalogue cytoskeleton and membrane properties of various subsets of normal human lymphocytes.